Metabolic Endotoxemia: One Root Cause of Many Diseases of Affluence

Welcome to The Perfect Stool: Understanding and Healing the Gut Microbiome. This is your host, Lindsey Parsons. And today I'm gonna be talking about a topic that may be unfamiliar, but is deeply connected with a lot of gut issues and which causes chronic inflammation and contributes to numerous other chronic health conditions common in the developed world. And that is metabolic endotoxemia. But before I do that, if you have haven't yet followed or subscribed to the show, be sure to do so. If you want to get transcripts of the podcast, pop over to my website, HighDesertHealthCoaching.com, and sign up for my newsletter. You'll also get my free ebooklet, Finding Your Root Cause Through Stool and Organic Acids Testing. And if you haven't yet done my quiz on which stool test would help you get to your root cause, you can find a link in the show notes and take that. Now on to the show. So what is metabolic endotoxemia? You may have heard that bacteria are divided into two groups, gram-positive and gram-negative. Gram-negative bacteria are surrounded by an outer membrane containing something called lipopolysaccharide, or LPS, and gram-positive bacteria lack that same outer membrane. So when you stain them, when you look under a microscope, they look different than gram-negative ones. So you may know that the two primary phyla of bacteria in the human gut are Firmicutes, which are gram-positive, and Bacteroidetes, which are gram-negative. Then the next two largest phyla are Proteobacteria, which are gram-negative, and Actinobacteria, which are gram-positive. Most of the major bacterial gut pathogens that you've heard of are gram-negative proteobacteria like Salmonella, E. coli, although most types of E. coli are not pathogenic, and Campylobacter. And this is probably logical because they're facultative anaerobes, meaning they can live in the presence of oxygen, hence it's easy to pass them between people and make you sick. So endotoxins are toxins in the bacterial cell wall of gram-negative bacteria. Which are released when the cell disintegrates upon its death, and they're also released in much smaller amounts when they're alive. And this endotoxin is composed mainly of LPS, or lipopolysaccharide, which activates the inflammatory response in, in humans. So even small amounts of LPS in the blood from a bacterial infection can elicit an inflammatory response and trigger the release of inflammatory cytokines or chemical messengers, which leads to low-grade chronic inflammation. So to put it all together, metabolic endotoxemia is a diet-induced 2 to 3-fold increase in plasma LPS levels, and it happens after eating, so it's called postprandial metabolic endotoxemia. So in other words, you eat a meal and mostly dead bacterial body parts start escaping out of your gut and sparking off inflammation. So as you may be guessing, something that goes hand in hand with metabolic endotoxemia is intestinal permeability. Aka leaky gut. I did an entire episode on leaky gut, which is episode 24 from March of 2020, so you can listen to that to get the lowdown. But to summarize briefly, leaky gut can come from an overgrowth of the very proteobacteria that you don't want escaping out of your gut, as in SIBO, small intestine bacterial overgrowth, from certain foods that contain lectins, from added sugar and fructose, alcohol nutrient deficiencies, chronic stress, smoking, toxin overload, and dysbiosis. So there's lots of ways that you can end up with a leaky gut. So what conditions are associated with metabolic endotoxemia? The consequences are many. Symptoms and diseases that are associated with it include insulin resistance, obesity, type 2 diabetes, non-alcoholic fatty liver disease, chronic kidney disease, atherosclerosis, chronic constipation, low testosterone, chronic pain, cognitive decline, memory loss, appetite disorders, depression, and anxiety. It can also promote autoimmunity and suppress the activity of your thyroid and cause autoimmune thyroid disease, which is Hashimoto's thyroiditis if you're hypothyroid, and Graves' disease if you're hyperthyroid. Endotoxemia also plays a role in chronic fatigue syndrome and is associated with markers seen in early Parkinson's disease patients. So there's a number of causes beyond just a leaky gut for metabolic endotoxemia, and many of these causes also cause the gut to be leaky. So it's all intermingled, as you'll see. The first is a high-fat diet, but mind you, in studies these were typically high junk food diets as well. So I don't think we can assume that this applies to a carefully constructed ketogenic diet, for example. Fructose consumption is another cause, but this is referring to high fructose corn syrup and other added fructose in foods and consumed in high quantities in the absence of fiber nutrients that are found in fruit. SIBO is another cause of metabolic endotoxemia, and it turns out that the primary bacteria in people with a positive hydrogen breath test, which is a diagnostic tool for SIBO, are the Enterobacteraceae, which are gram-negative. And the most common specific overgrown bacteria found in SIBO include Escherichia coli, which is gram-negative, Enterococcus species, which are gram-positive, Klebsiella pneumoniae, which is gram-negative, and Proteus mirabilis, which is gram-negative. So the majority of these are gram-negative and produce LPS, and just having an overabundance of these gram-negative proteobacteria will itself cause leaky gut. And then these are the bacteria that have the LPS causing the metabolic endotoxemia. Chronic alcohol consumption can also be a cause. This happens because alcohol can increase pathogenic bacteria and decrease beneficial bacteria, and also because the metabolism of alcohol generates reactive oxygen species, also known as oxidative stress, which can damage gut cells and impair gut barrier function, allowing for the translocation of LPS into the bloodstream. Periodontal disease is another possible cause because in periodontal disease, you have an overgrowth of harmful bacteria in the oral microbiome, which of course leads into the gut microbiome and can cause dysbiosis and intestinal permeability and then leakage of LPS. And the primary pathogens in periodontal disease are also gram-negative. This one doesn't seem fair, but aging itself can also lead to end— metabolic endotoxemia. Because it's known that as we age, our gut diversity decreases, which can then contribute to an imbalance in the gut microbiota and promote the growth of pathogenic bacteria that produce endotoxins. Aging is also associated with an increase in intestinal permeability, which may be in part due to age-related changes in gut physiology, such as decreased motility. In addition, aging is associated with a decline in organ function, including the liver and kidneys, which are important for detoxification and elimination of bacterial toxins. Impaired liver and kidney function can lead to an accumulation of those toxins contributing to metabolic endotoxemia. And finally, smoking causes metabolic endotoxemia in the same way that alcohol use does by creating dysbiosis and oxidative stress, which damages the gut barrier, creates permeability, and also impairs liver function, which can decrease clearance of LPS from the bloodstream, contributing to metabolic endotoxemia. So how do you stop it? First of all, if you're having lots of bloating, gas, or acid reflux, the primary symptoms of SIBO, that's the first thing to address. If you have recurrent SIBO, finding and addressing the root cause is important. And if it's autoimmune in nature, using prokinetic supplements. And no matter what the root cause, spacing out your meals and periodically using antimicrobials and some type of SIBO diet like low FODMAPs or the biphasic diet is usually necessary. I did an entire episode on recurrent SIBO. It's episode 83 from October of 2022, so check that out for more information. Then there are basic lifestyle interventions that can help you if you suspect that this is going on for you and you don't have obvious SIBO symptoms. So that's reducing saturated fats, eating a Mediterranean diet rich in fruits, veggies, nuts, and legumes, reducing omega-6 fatty acids found in oils like soybean, corn, cottonseed, sunflower, and peanut oils, and processed foods that are high in them. Then increasing cod liver and fish oils will help. And unless you're eating fatty fishes very regularly, like a few times a week, you may wanna think about incorporating a regular fish oil supplement in your regime. But look closely to make sure you're getting plenty of EPA and DHA in your fish oil because sometimes it's just like, you might get 1,000 milligrams of fish oil in a capsule, but only 300 milligrams of EPA and DHA. Whereas the highest quality fish oil supplements like ProOmega-2000, which you can find in my FullScript dispensary, has 1,000 milligrams of EPA and DHA in one capsule. Then eating lots of probiotic foods or taking probiotics can also be helpful, and incorporating prebiotic-rich foods in your diet or supplementing with prebiotics like inulin and FOS, um, which is fructooligosaccharides. So that's not great if you have recurrent SIBO, but inulin and FOS are found in chicory root, Jerusalem artichoke, onions, garlic, asparagus, jicama, and bananas, among other things. And those two prebiotics help feed beneficial lactobacilli and bifidobacteria. Which can then crowd out the pathogenic bacteria. Then avoiding sugar, excessive salt, and surfactants found in processed foods like polysorbate 80, mono and diglycerides, soy lecithin, and carrageenan is also helpful. And then if you suspect your gut immune system isn't working well because you keep getting bouts of different gut pathogens, or you know based on your GI MAP results or other stool test results that your secretory IgA is low, which is your gut immune defense system, you can use colostrum or its more purified derivative without any dairy serum bovine immunoglobulin powder. Examples of this are Mega IgG 2000 by Microbiome Labs and Immuno GG SBI powder by Biotics Research and IgG-I Shield by Designs for Health to protect yourself against the pathogenic bacteria. And then nutrients to support secretory IgA production include omega-3 fatty acids, glutathione, glycine, glutamine, phosphatidylcholine, vitamin C, and zinc. And then it's also known that S. boulardii probiotics bring up secretory IgA.. And you can also support your mucin production because the mucin layer is what protects the gut barrier, which is just one cell thick, with amino acids like L-threonine, L-proline, L-cysteine, and L-serine. These are all found in Microbiome Labs Mega Mucosa, which is designed to support that mucin layer. And then the most studied tool for helping with endotoxemia are the spore-based probiotics. Microbiome Labs did a 30-day study with their spore-based probiotic MegaSporeBiotic, which was published in the World Journal of Gastrointestinal Pathophysiology, that showed that it reduced postprandial meaning after a meal, dietary endotoxemia by 42% and reduced triglycerides by 24%. Whereas in the placebo group, there was a 36% rise in endotoxin and a 5% decrease in triglycerides. So I hope that was a helpful introduction to one of the likely drivers of chronic disease that has its origins in your gut microbiome. And if you're struggling with some type of chronic disease, chronic inflammation, bloating, constipation, diarrhea, soft stool, acid reflux, et cetera, and wanna get to the bottom of it, That's what I help my clients with. You're welcome to set up a free 30-minute breakthrough session if you think you might like to sign up for a 3 or 5 session package, or I offer individual consultations as well. You can find links for those in the show notes. If you'd like to support the show, you can make a regular donation on Patreon or buy vetted high-quality supplements from my Fullscript or Well-Evate dispensaries, or give me a 5-star review on Apple Podcasts. To reach out to me in other ways, I have a Gut Healing Facebook group for asking questions, or I'm on Instagram, Pinterest, and Twitter, and now TikTok. Links for all Those are in the show notes or on my website, highdigestionhealthcoaching.com. Thanks for listening, and here's wishing you all the perfect stool.